Backgrounds and Aims: Matrix metalloproteinases have been known to be associated with the pathogenesis of in-stent restenosis after coronary intervention through facilitate smooth muscle cell proliferation and migration. We investigated the association between MMP-3, MMP-9 gene polymorphisms and target lesion revascularization (TLR). Methods and Results: This is a substudy of Seoul-Catholic Gene [SeCaGene] study, which is a prospective study on genetic polymorphisms to elucidate the complex genetic trait of cardiovascular disease. From April 2004 to February 2007, 764 patients who underwent drug-eluting stent (DES) implantation with complete six month clinical follow up were included for this study. Genotypes of 3 SNP sites of MMP-3(rs602128, rs476762, rs650108) and 3 SNP sites of MMP-9(rs17576(Q278R), rs2250889(R573P),rs2274756(R667Q)) were identified. All MMP-9 polymorphisms were non-synonymous SNP���s. The minor allele frequency was 0.33 for rs602128, 0.12 for rs476762 , 0.44 for rs650108, 0.32 for rs17576, 0.28 for rs2250889 and 23.5 for rs2274756. TLR due to in-stent restenosis were performed in 56 patients at 6 month after initial stenting. Presence of minor allele of rs476762 (T���A) and rs650108 (A���G) MMP-3 polymorphism were significant risk factor for TLR during the six month follow-up period in univariate analysis (rs476762(A allele) : OR, 1.98; 95% CI, 1.10 to 3.54;, P=0.020, rs650108(G allele): OR, 2.16; 95% CI, 1.07 to 4.35; P=0.028). In multivariate analysis including the common cardiovascular risk factors such as male sex, age, diabetes, hypertension, dyslipidemia and smoking, rs650108 (A���G) was associated with TLR with marginal statistical significance (P=0.11). Other studied genes did not show significant associations with TLR. Co-existence of the both rs476762(A allele) and rs650108(G allele) was not associated with TLR. Conclusion: The genotypes of rs602128, rs476762 of MMP-3 and rs17576, rs2250889, rs2274756 of MMP-9 were not associated with TLR after DES implantation. However, minor allele of rs650108(A���G) MMP-3 polymorphisms was associated with TLR with marginal statistical significance. Further study on the functional significance of this polymorphism is necessary.